Only about 15% of the known compounds lend themselves to analysis by gas chromatography owing to insufficient volatility or thermal instability. Liquid column chromatography, on the other hand, does not have these limitations. The interchange or combination of solvents can provide special selectivity effects that are absent when the mobile phase is a gas. Ionic compounds, labile naturally occurring compounds, polymers, and high molecular weight polyfunctional compounds are conveniently analyzed by liquid chromatography. While liquid flow in traditional liquid chromatography was achieved by gravity, modern liquid column chromatography uses high pressure pumps with relatively short narrow-bore columns containing small particles of packing.
One of the most important parts in a liquid chromatography setup is the solvent delivery system. Such a system must be able to precisely deliver a solvent (or a mixture of different solvents) over a relatively broad flow range. Sampling valves are essential components of this solvent delivery system, allowing the sample to be reproducibly introduced into the column without significant interruption of the flow. Sampling valves are also used for connecting and disconnecting the chromatography column to the process piping (e.g., for flushing purposes).
An exemplary prior art liquid chromatography valve setup is schematically depicted in FIGS. 1A-1D. FIG. 1A shows a valve assembly 10 comprising valves 12a, 12b, 14a, 14b, 16a, and 16b. Liquid enters the system from the entrance process piping 20 and can be directed through the valve assembly 10 by controlling the afore-mentioned valves as will be later explained. The system gives the user the flexibility to have the product fluid flow through a chromatography column (not shown) in a forward (FIG. 1B) or reverse (FIG. 1C) direction, or the product fluid can be made to completely bypass the column (FIG. 1D). Liquid leaves the valve assembly through the exit process piping 22.
Fluid can flow through the prior art valve assembly 10 depicted in FIG. 1A in any one of the three directions depicted in FIGS. 1B-1D. The fluid flow is represented by arrows 25 in these figures. In FIG. 1B, which represents the forward product flow through the column, valve 14a is opened allowing the fluid to flow from the process piping into the valve assembly 10. Valve 16a is also opened allowing the fluid to flow into the chromatography column (not shown). The fluid returns from the chromatography column passing through valve 16b and reentering the valve assembly. The fluid leaves the valve assembly passing through valve 14b on its path back to the process piping. Valves 12a and 12b remain closed during this process. According to the reverse process flow depicted in FIG. 1C, fluid entering the valve assembly 10 from the process piping can flow through valves 12a and 16b into the column, returning from the column through valve 16a, and exiting the valve assembly through valve 12a back through the process piping. Valves 14a and 14b remain closed during this process. The column may be bypassed altogether according to the process flow depicted in FIG. 1D, where the liquid entering into the valve assembly from the process piping encounters opened valves 12a, 14a, 12b and 14b, exiting the valve assembly without entering the chromatography column which remains inaccessible by closing valves 16a and 16b.
Prior art liquid chromatography valve assemblies like the one described above are typically fabricated using either six independent valves or two two-way diverter valves with two independent valves, connected either by sanitary tri-clams or welded to tee fittings. The problem encountered with these systems, which is especially prevalent in those using the tee fittings, is the existence of dead-legs. Dead-legs are areas of liquid that have become trapped in the valve assembly when the flow of liquid in a particular branch of the system is halted. In dead-legs, fluid can stagnate causing contaminants to accumulate or micro-organisms to grow. This presents a serious problem in liquid chromatography where such contaminants can adversely affect the results of a particular analysis. Hence the need for a diverter type valve assembly in which all flow compartments are shared and fully flushed when a flow through valve is opened clearly exists.
Diverter valves are not particularly new, and, in fact, the prior art includes many examples of different types of these valves. An example of such a valve is described in U.S. Pat. No. 5,273,075 to R. A. Skaer entitled DIVERTER VALVE. The valve described in this patent comprises a diaphragm type valve with a single inlet port and two outlet ports, and is set up such that the flow of fluids can be directed from the inlet port to one or the other outlet ports. The valve operates by closing a diaphragm against an edge or weir of a partition with the valve housing which prohibits fluid flow to the one port while accommodating flow to the other port. This specific diverter valve is made for use with systems that require only a single inlet port and no more than two outlet ports, and hence, such a valve system would not accommodate the intricate plumbing necessary to operate a liquid chromatography system. Moreover, the valve assembly described above requires specialized components, including a specific housing that itself is the subject of a U.S. patent (U.S. Pat. No. 5,427,150 to Skaer et al. Entitled HOUSING FOR A DIVERTER VALVE).
The problem with most prior art diverter valve assemblies revolves around the fact that they are not manufactured out of a single block of material. These valve assemblies are therefore relatively expensive to manufacture, and are, in general, difficult to clean in place due to the dead-legs present when tee fittings are used in them. When these valves are fully assembled, they also take up a large volume in space requiring more installation volume. Since it is the object of most bio technology and pharmaceutical firms to minimize dead-legs and to make process piping and valve assemblies as compact as possible, a new valve assembly which ameliorates these difficulties is sorely needed.
It is therefore an object of the present invention to provide a compact unitarily formed diverter type valve system for use in liquid chromatography in which dead-legs between the valves are eliminated and in which the installation space needed for the system is minimized.